Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Adv Sci (Weinh). 2024 May;11(20):e2306297. doi: 10.1002/advs.202306297. Epub 2024 Mar 13.
Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.
胃肠道（GI）动力障碍在炎症性肠病（IBD）患者中非常普遍，但其潜在的致病作用尚不清楚。在此，研究了 GI 运动障碍在结肠炎发病机制中的作用和机制。慢性便秘（CC）患者的结肠黏膜炎症增加。由于肠道微生物群的存在，由于遗传突变或化学刺激引起 GI 运动障碍的小鼠易患结肠炎。GI 运动障碍显着降低乳杆菌属的丰度，并增加阿克曼氏菌属的丰度。由于共轭亚油酸的转化受到损害，乳杆菌属的减少导致亚油酸的积累。亚油酸的积累通过诱导巨噬细胞浸润和巨噬细胞中促炎细胞因子的表达来抑制 Treg 细胞分化并增加结肠炎易感性。CC 和 IBD 患者也观察到乳杆菌属和阿克曼氏菌属的异常，接受 CC 患者粪便微生物群的小鼠对结肠炎的易感性增加。这些发现表明，GI 运动障碍通过调节微生物群的组成和促进亚油酸积累使宿主易患结肠炎。靶向调节微生物群和亚油酸代谢可能有望保护运动障碍患者免受肠道炎症的影响。
